Acquired Immune Deficiency Syndrome (AIDS) remains one of the leading causes of morbidity and mortality in the world. In 2011, the United Nations reported that 1.7 million people died from AIDS-related illnesses. According to the United Nations Programme on AIDS, it was estimated that, as of 2011, 34.2 million people worldwide were infected with human immunodeficiency virus (HIV), including 2.5 million people newly infected with HIV in 2011. amfAR, the Foundation for AIDs Research, reported that more than 60 million people have contracted HIV and approximately 30 million people have died of HIV-related causes since the epidemic began.
AIDS deaths reportedly have fallen for five years in a row, down from 2.3 million in 2005 and 2006 to 1.7 million in 2011. With the successful curtailment of the proliferation of HIV in the blood through the introduction of highly-active antiretroviral therapy (HAART), the population of people infected with HIV now live longer, which has led to the emergence of latent HIV brain infections and associated cognitive decline as a major public health threat. However, current HAART treatment does not treat latent HIV brain disease. HIV is known to cross the blood-brain barrier and enter the nervous system early in systemic infection. It has been reported that neurologic disease is the first manifestation of symptomatic HIV infection in many patients, and that the majority of patients with advanced HIV disease have clinically evident neurologic dysfunction. Numerous neurological complications are associated with AIDS, including AIDS dementia complex (ADC), which is also known as HIV-associated dementia (HAD), HIV encephalopathy, and HIV-associated neurocognitive disorder.
Curcumin, a natural product isolated from the rhizome of Curcuma longa, has been investigated as a possible HIV treatment. Curcumin has demonstrated a wide range of biological activity, including antioxidant, anti-inflammatory, and anticancer. (Du et al., European J. Medicinal Chemistry, 41:213-218 (2006).) Curcumin also inhibits the enzyme alpha-glucosidase and HIV integrase, which are required by HIV-1 to infect human cells. However, clinical studies of curcumin for HIV treatment have produced unsatisfactory results, which are believed to be due, at least in part, to the rapid metabolism of orally administered curcumin by the liver into metabolites that are inactive and incapable of crossing the blood-brain barrier to become available to the brain (Anand et al. 2007). As such, curcumin does not have the ability to reach the brain in sufficient quantities and duration to protect the brain from HIV-1 toxicity.
In addition, curcumin is poorly absorbable by mouth because it is not very lipophilic (Anand et al. 2007). Animal studies have largely relied on intraperitonial (i.e., injecting inside the abdomen) and intracranial (i.e., injecting into the brain) administrations to achieve biological effects that are seen in in vitro (i.e., direct tissue) treatments. Moreover, previous in vitro studies of curcumin for HIV inhibition have shown that larger concentrations of curcumin (i.e., in micrograms) are needed to exact pharmacological action.
Therefore, a need remains for a composition that is administrable through routes that are feasible for daily human use for HIV treatment and that can reach the brain site for prevention of direct and indirect HIV-mediated toxicity.